O-08: NEUROCOGNITIVE IMPAIRMENT IN UGANDAN CHILDREN WITH SICKLE CELL ANEMIA COMPARED TO NON-SICKLE SIBLINGS
Authors: BANGIRANA P., IDRO R., OPOKA R., MUNUBE D., MUPERE E., KASIRYE P., GREEN N., BOEHME A.
Journal: HemaSphere (2022)

Purpose: Sickle cell anemia (SCA) increases childhood risk of neurocognitive impairment from severe anemia and vascular brain injury. We hypothesized that impaired neurocognitive function was more prevalent in Ugandan children with SCA than in their non-SCA siblings. Materials and methods: In the BRAIN SAFE 1 cross-sectional study (Green NS, 2019), a sample of children ages 1-12 years were randomly selected from Mulago Hospital SCA clinic in Kampala. Their neurocognitive function was compared to that of unaffected siblings using age-appropriate tests: Mullen Scales of Early Learning (Mullen) for children under age five and Kaufman Assessment Battery for Children, second edition (KABC-II) for ages 5-12. Raw scores were converted into age-adjusted Z-scores compared to established community controls; Z-scores -2 or lower were categorized as impaired neurocognitive function. Relationships between key variables and neurocognitive impairment (impaired vs. not impaired) were evaluated by logistic regression. Results: Overall, 369 participants were evaluated: 242 with SCA (mean age 5.44 ±2.9 years) and 127 non-SCA siblings (mean age 7.8± 3.3 years; p<0.0001). Mean hemoglobin was lower in SCA participants (7.3 ±1.02 g/dl vs. 12.1 ±1.45; p=0.0001); the groups were similar by sex (p=0.33). Neurocognitive impairment was present in 27 (11.2%) of children with SCA compared to 8 (6.3%) of non-SCA siblings. Children with SCA had lower median neurocognitive Z-scores compared to siblings (-0.62 vs. 0.30; p<0.0001) overall and for each age group tested: ages 1-4 years (-0.35 vs. 0.53, p=0.0001) and 5-12 (-0.88 vs. 0.25, p=0.0001) (Figure). SCA participants had higher odds of impairment (OR 1.88, 95%CI 0.83-4.27) compared to non-SCA; this relationship became stronger after accounting for age and caregiver education (secondary/tertiary school vs. primary/none) (aOR 5.07 (1.69-15.1)) (Table). After accounting for SCA status, increased age accounted for 50% increased risk of neurocognitive impairment (aOR 1.50, 95%CI 1.29-1.75). Overall, higher caregiver education modestly reduced the odds of neurocognitive impairment (OR 0.64 (0.23-1.72)). In participants with SCA, prior stroke or elevated TCD velocity each strongly predicted cognitive dysfunction (OR 6.60 (2.14-20.4) or 2.90 (1.09-7.74), respectively. These associations strengthened after accounting for age, hemoglobin and malnutrition (Table). Among siblings, age was significantly associated with impaired cognition (aOR 3.48 (1.00-12.1)), even after accounting for sex and hemoglobin (data not shown). Conclusion: In this Kampala-based sample and accounting for age, children with SCA had 4-fold greater odds of neurocognitive impairment compared to non-SCA siblings. For participants with SCA, major predictors of impairment were age, prior stroke and elevated TCD arterial velocity. These abnormalities were commonly found, translating into significant disease-associated morbidity and potential long-term disability. A treatment trial with hydroxyurea is underway to assess impact on neurocognitive function and reduction of stroke risk. Supported by R21HD089791 and 3R21HD089791-02S (Idro, Green)Children with SCA score lower on neurocognitive testing than their non-SCA siblings in both age groups sampled.Table. Multivariable Regression Analyses evaluating Odds of Neurocognitive Dysfunction in Children Ages 1-12 years with SCA (n=242) Compared to Non-SCA Siblings (n=127). The authors do not declare any conflict of interest